Chemistry Faculty Publications and PresentationsCopyright (c) 2015 Boise State University All rights reserved.http://scholarworks.boisestate.edu/chem_facpubs
Recent documents in Chemistry Faculty Publications and Presentationsen-usSun, 02 Aug 2015 01:31:49 PDT3600GAMPMS: Genetic Algorithm Managed Peptide Mutant Screeninghttp://scholarworks.boisestate.edu/chem_facpubs/95
http://scholarworks.boisestate.edu/chem_facpubs/95Fri, 31 Jul 2015 11:29:46 PDT
The prominence of endogenous peptide ligands targeted to receptors makes peptides with the desired binding activity good molecular scaffolds for drug development. Minor modifications to a peptide's primary sequence can significantly alter its binding properties with a receptor, and screening collections of peptide mutants is a useful technique for probing the receptor–ligand binding domain. Unfortunately, the combinatorial growth of such collections can limit the number of mutations which can be explored using structure-based molecular docking techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a genetic algorithm to conduct a heuristic search of the peptide's mutation space for peptides with optimal binding activity, significantly reducing the computational requirements of the virtual screening. The GAMPMS procedure was implemented and used to explore the binding domain of the nicotinic acetylcholine receptor (nAChR) -isoform with a library of 64,000 α-conotoxin (α-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared with a virtual screening procedure that used AutoDock to predict the binding affinity of each of the α-CTx MII peptide mutants with the -nAChR. The GAMPMS implementation performed AutoDock simulations for as few as 1140 of the 64,000 α-CTx MII peptide mutants and could consistently identify a set of 10 peptides with an aggregated binding energy that was at least 98% of the aggregated binding energy of the 10 top peptides from the exhaustive AutoDock screening.
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Thomas Long et al.Excitonic AND Logic Gates on DNA Brick Nanobreadboardshttp://scholarworks.boisestate.edu/chem_facpubs/94
http://scholarworks.boisestate.edu/chem_facpubs/94Mon, 02 Mar 2015 12:24:02 PST
A promising application of DNA self-assembly is the fabrication of chromophore-based excitonic devices. DNA brick assembly is a compelling method for creating programmable nanobreadboards on which chromophores may be rapidly and easily repositioned to prototype new excitonic devices, optimize device operation, and induce reversible switching. Using DNA nanobreadboards, we have demonstrated each of these functions through the construction and operation of two different excitonic AND logic gates. The modularity and high chromophore density achievable via this brick-based approach provide a viable path toward developing information processing and storage systems.
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Brittany L. Cannon et al.Statistical Thermodynamics of Material Transport in Nonisothermal Suspensionshttp://scholarworks.boisestate.edu/chem_facpubs/93
http://scholarworks.boisestate.edu/chem_facpubs/93Thu, 05 Feb 2015 13:49:37 PST
An approach to the transport of material in a temperature gradient is outlined using nonequilibrium thermodynamics theory. The model is applicable to the thermophoresis of colloids and nanoparticles in systems with limited miscibility. Component chemical potentials in binary systems are calculated using statistical mechanics. The local pressure distribution is obtained using the condition of local thermodynamic equilibrium around the suspended particle. The Laplace contribution of the local pressure distribution within the layer of liquid surrounding the particle leads to a size dependence that is consistent with empirical data. The contribution of Keezom interaction to the thermodiffusion coefficient is calculated using empirical values of the thermodiffusion coefficient for silica particles in water and acetonitrile. The resulting interaction energies are consistent with those found in the literature.
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Semen Semenov et al.Evolution of Acyl-Substrate Recognition by a Family of Acyl-Homoserine Lactone Synthaseshttp://scholarworks.boisestate.edu/chem_facpubs/92
http://scholarworks.boisestate.edu/chem_facpubs/92Wed, 10 Dec 2014 14:18:54 PST
Members of the LuxI protein family catalyze synthesis of acyl-homoserine lactone (acyl-HSL) quorum sensing signals from S-adenosyl-L-methionine and an acyl thioester. Some LuxI family members prefer acyl-CoA, and others prefer acyl-acyl carrier protein (ACP) as the acyl-thioester substrate. We sought to understand the evolutionary history and mechanisms mediating this substrate preference. Our phylogenetic and motif analysis of the LuxI acyl-HSL synthase family indicates that the acyl-CoA-utilizing enzymes evolved from an acyl-ACP-utilizing ancestor. To further understand how acyl-ACPs and acyl-CoAs are recognized by acyl-HSL synthases we studied BmaI1, an octanoyl-ACP-dependent LuxI family member from Burkholderia mallei, and BjaI, an isovaleryl-CoA-dependent LuxI family member from Bradyrhizobium japonicum. We synthesized thioether analogs of their thioester acyl-substrates to probe recognition of the acyl-phosphopantetheine moiety common to both acyl-ACP and acyl-CoA substrates. The kinetics of catalysis and inhibition of these enzymes indicate that they recognize the acyl-phosphopantetheine moiety and they recognize non-preferred substrates with this moiety. We find that CoA substrate utilization arose through exaptation of acyl-phosphopantetheine recognition in this enzyme family.
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Quin H. Christensen et al.Medicinal History of North American <em>Veratrum</em>http://scholarworks.boisestate.edu/chem_facpubs/91
http://scholarworks.boisestate.edu/chem_facpubs/91Wed, 01 Oct 2014 15:04:16 PDT
Plants belonging to the genus Veratrum have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in Veratrum species, some of which are potent bioactives. This review discusses Veratrum species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus Veratrum (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the Veratrum plants of North America and the medicinal uses of their bioactive steroidal alkaloids.
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Christopher M. Chandler et al.Theory of Soret Coefficients in Binary Organic Solventshttp://scholarworks.boisestate.edu/chem_facpubs/90
http://scholarworks.boisestate.edu/chem_facpubs/90Mon, 28 Apr 2014 14:39:30 PDT
Thermodiffusion in binary molecular liquids is examined using the nonequilibrium thermodynamic model, where the thermodynamic parameters are calculated using equations based on statistical mechanics. In this approach, thermodiffusion is quantified through the variation in binary chemical potential and its temperature and concentration dependence. The model is applied to solutions of organic solvents, in order to compare our theoretical results to experimental results from the literature. A measurable contribution of the orientation-dependent Keezom interaction is shown, where the possible orientations are averaged using the Boltzmann weighting factor. Calculations of enthalpies of evaporation from the model yield good agreement with experimental values from the literature. However, calculations of the associated energetic parameters were several times larger than those reported in the literature from numeric simulations of material transport.
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Semen Semenov et al.Homology Modeling and Molecular Docking for the Science Curriculumhttp://scholarworks.boisestate.edu/chem_facpubs/89
http://scholarworks.boisestate.edu/chem_facpubs/89Mon, 31 Mar 2014 11:18:08 PDT
DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that allows users to utilize a readily accessible computational tool to explore biomolecules and their interactions. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular structure creation, ligand binding calculations, and visualization of docking results. A student procedure is provided that illustrates the use of DockoMatic to create a homology model for the amino propeptide region (223 amino acids with two disulfide bonds) of collagen α1 (XI), followed by molecular docking of the commercial drug Arixtra® to the homology model of α1 (XI), and finally, analysis of the results of the docking experiment. The activities and Supporting Information described are intended to educate students in the use of computational tools to create and investigate homology models for other systems of interest and to train students to perform and analyze molecular docking studies. The tutorial also serves as a foundation for investigators seeking to explore the viability of using computational biochemistry to study their receptor–ligand binding motifs.
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Owen M. McDougal et al.Modeling S<sub>N</sub>2 and E2 Reaction Pathways and Other Computational Exercises in the Undergraduate Organic Chemistry Laboratoryhttp://scholarworks.boisestate.edu/chem_facpubs/88
http://scholarworks.boisestate.edu/chem_facpubs/88Thu, 17 Oct 2013 16:40:21 PDT
Computational chemistry techniques have become increasingly important tools for chemists seeking to address scientific questions. As such, it is important that undergraduate chemistry students develop competence in this emerging field of chemistry. One strategy to gain proficiency involves exposing students to computational methods of increasing depth and complexity during each year of their laboratory curriculum, rather than solely at late stages of their education. The computational chemistry exercises described herein are designed to be completed in one introductory-level organic chemistry laboratory period, and they build upon concepts covered in traditional organic lecture and lab curricula. Students generate electrostatic potential maps for substituted acetic acids to analyze bond polarity and pKa, model acetate to explore resonance, and conduct conformation searches for monosubstituted cyclohexanes to examine the influence of sterics on conformational preference. They also generate reaction coordinate diagrams for substitution and elimination reactions between 2-bromobutane and various alkoxide bases. Students are asked to examine the energetics of starting materials, possible products, and theoretical transition states. All aspects of the exercises align with traditional topics, and thus reinforce their significance.
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Clifford M. Csizmar et al.DockoMatic 2.0: High Throughput Inverse Virtual Screening and Homology Modelinghttp://scholarworks.boisestate.edu/chem_facpubs/87
http://scholarworks.boisestate.edu/chem_facpubs/87Tue, 24 Sep 2013 08:56:20 PDT
DockoMatic is a free and open source application that unifies a suite of software programs within a user-friendly graphical user interface (GUI) to facilitate molecular docking experiments. Here we describe the release of DockoMatic 2.0; significant software advances include the ability to (1) conduct high throughput inverse virtual screening (IVS); (2) construct 3D homology models; and (3) customize the user interface. Users can now efficiently setup, start, and manage IVS experiments through the DockoMatic GUI by specifying receptor(s), ligand(s), grid parameter file(s), and docking engine (either AutoDock or AutoDock Vina). DockoMatic automatically generates the needed experiment input files and output directories and allows the user to manage and monitor job progress. Upon job completion, a summary of results is generated by Dockomatic to facilitate interpretation by the user. DockoMatic functionality has also been expanded to facilitate the construction of 3D protein homology models using the Timely Integrated Modeler (TIM) wizard. The wizard TIM provides an interface that accesses the basic local alignment search tool (BLAST) and MODELER programs and guides the user through the necessary steps to easily and efficiently create 3D homology models for biomacromolecular structures. The DockoMatic GUI can be customized by the user, and the software design makes it relatively easy to integrate additional docking engines, scoring functions, or third party programs. DockoMatic is a free comprehensive molecular docking software program for all levels of scientists in both research and education.
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Casey Bullock et al.Improved Extraction and Complete Mass Spectral Characterization of Steroidal Alkaloids from <em>Veratrum californicum</em>http://scholarworks.boisestate.edu/chem_facpubs/86
http://scholarworks.boisestate.edu/chem_facpubs/86Tue, 24 Sep 2013 08:40:18 PDT
Four steroidal alkaloids extracted from the roots and rhizomes of Veratrum californicum were separated by high performance liquid chromatography (HPLC) and identified using high resolution electrospray ionization time of flight tandem mass spectrometry (ESI-TOF-MS/MS) as veratrosine, cycloposine, veratramine, and cyclopamine. This paper compares ethanol and benzene as extraction solvents, HPLC solvent conditions leading to good separation of steroidal alkaloids, and MS/MS fragmentation patterns for the four steroidal alkaloids which have been released to the public database MassBank.jp. The reported Soxhlet extraction method nearly triples the recovery of steroidal alkaloids from V. californicum.
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Christopher M. Chandler et al.Rejoinder to the Reply to a Comment by S.N. Semenov and M.E. Schimpf on ‘Role of the Velocity Frame of Reference in Thermodiffusion in Liquid Mixtures’, Philosophical Magazine Vol. 92, 705 (2012), by M. Eslamian, C.G. Jian and M.Z. Saghirhttp://scholarworks.boisestate.edu/chem_facpubs/85
http://scholarworks.boisestate.edu/chem_facpubs/85Mon, 16 Sep 2013 10:14:22 PDTSemen N. Semenov et al.Parathion Hydrolysis Revisited: In Situ Aqueous Kinetics by <sup>1</sup> H NMRhttp://scholarworks.boisestate.edu/chem_facpubs/84
http://scholarworks.boisestate.edu/chem_facpubs/84Tue, 10 Sep 2013 11:09:43 PDT
The kinetics of parathion (PTH) decomposition into para-nitrophenolate (pNP) and O,O-diethylthiophosphate (DETP) were measured in high-pH aqueous solutions at 20 °C by proton nuclear magnetic resonance spectroscopy (1H NMR). Reaction rates were determined over a 16 h observation time, in solutions with NaOD concentrations of 5.33 mM, 33.33 mM, and 100 mM, with NaCl added to fix ionicity. The pseudo-first-order rate constants for these systems were determined to be 1.9 × 10–4 min–1, 1.4 × 10–3 min–1, and 3.8 × 10–3 min–1 respectively. The slope of the linear plot of these rates against OD– concentration yielded the second-order hydrolysis rate constant 3.90 × 10–5 mM–1 min–1, valid over this pH range from 10.5 to 13. The data agree with some, and contradict other, earlier work. Our fitting procedure included background levels and allowed us to not only obtain reliable kinetic results but also to measure residual pNP and DETP impurity levels.
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Emma C. Wanamaker et al.A Green Approach to Separate Spinach Pigments by Column Chromatographyhttp://scholarworks.boisestate.edu/chem_facpubs/83
http://scholarworks.boisestate.edu/chem_facpubs/83Mon, 08 Jul 2013 10:11:31 PDT
Chromatography has been a fundamental technique used for chemical separation that dates back to the 1850s. Specifically, column chromatography, typically taught in introductory organic chemistry laboratories, traditionally involves the use of halogenated or harmful solvents, which novice students often overuse. This situation runs contrary to the principles of responsible chemical and waste management emphasized by the green chemistry movement. Since this movement began, conventional means of separation using harmful solvents have been modified to emphasize the need for safer, less hazardous materials and the generation of such waste. The current experiment emphasizes the green chemical principles of renewable feedstocks and recycling to minimize waste, while simultaneously introducing or reinforcing common organic techniques, including solvent extraction, column chromatography, and thin-layer chromatography for the isolation and identification of photosynthetic pigments from spinach leaves. Students gain practical experience processing plant material to isolate and identify the pigments, β-carotene, xanthophylls, and chlorophyll a, using the solvents hexane and acetone. This experiment was designed for use as a standalone single-session lab or, alternatively, it can be coupled with an experiment to recycle waste acetone to further emphasize sustainable practices.
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Aubrey Johnston et al.Synthesis, Properties and Crystal Structure of the 2,4-Dichlorophenyl-Cyanoxime: A Powerful Carbonyl Reductase Inhibitorhttp://scholarworks.boisestate.edu/chem_facpubs/82
http://scholarworks.boisestate.edu/chem_facpubs/82Fri, 29 Mar 2013 14:40:37 PDT
The compound 2,4-dichlorophenylcyanoxime (later H(2,4-diCl-PhCO)) has significance in its possible application in cancer chemotherapy treatments since it acts as an inhibitor of the human carbonic reductase. This enzyme decreases the effectiveness of anthracycline drug treatment of some types of cancer. The compound was synthesized in high yield at ambient conditions from 2,4-dichlorophenylacetonitrile, using gaseous methylnitrite. The compound was characterized by means of UV–visible, IR, 1H, 13C NMR spectroscopy and X-ray analysis. The cyanoxime crystallizes in a monoclinic space group P21/c (#14) with unit cell constants: a = 3.7587(9) Å, b = 30.087(7) Å, c = 7.6874(17) Å, β = 96.163(3)°; V = 864.3(3) Å3, Z = 4. The structure was solved, using direct methods, to final R indices [I > 2σ (I)] R1 = 0.0551 (wR2 = 0.1217). The compound adopts a non-planar, trans-anti configuration with the value of the dihedral angle between the cyanoxime and dichlorophenyl planes equal to 50.61°.
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Michael Hilton et al.p<em>K</em><sub>a</sub> Determination of Histidine Residues in α-Conotoxin MII Peptides by <sup>1</sup>H NMR and Constant pH Molecular Dynamics Simulationhttp://scholarworks.boisestate.edu/chem_facpubs/81
http://scholarworks.boisestate.edu/chem_facpubs/81Thu, 28 Mar 2013 09:04:23 PDT
α-Conotoxin MII (α-CTxMII) is a potent and selective peptide antagonist of neuronal nicotinic acetylcholine receptors (nAChR’s). Studies have shown that His9 and His12 are signiﬁcant determinants of toxin binding aﬃnity for nAChR, while Glu11 may dictate diﬀerential toxin aﬃnity between nAChR isoforms. The protonation state of these histidine residues and therefore the charge on the α-CTx may contribute to the observed diﬀerences in binding aﬃnity and selectivity. In this study, we assess the pH dependence of the protonation state of His9 and His12 by 1H NMR spectroscopy and constant pH molecular dynamics (CpHMD) in α-CTxMII, α-CTxMII[E11A], and the triple mutant, α-CTxMII- [N5R:E11A:H12K]. The E11A mutation does not signiﬁcantly perturb the pKa of His9 or His12, while N5R:E11A:H12K results in a signiﬁcant decrease in the pKa value of His9. The pKa values predicted by CpHMD simulations are in good agreement with 1H NMR spectroscopy, with a mean absolute deviation from experiment of 0.3 pKa units. These results support the use of CpHMD as an eﬃcient and inexpensive predictive tool to determine pKa values and structural features of small peptides critical to their function.
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Owen M. McDougal et al.Comment on ‘‘Role of the Velocity Frame of Reference in Thermodiffusion in Liquid Mixtures’’ by M. Eslamian, C.G. Jiang and M.Z. Saghirhttp://scholarworks.boisestate.edu/chem_facpubs/80
http://scholarworks.boisestate.edu/chem_facpubs/80Thu, 15 Nov 2012 17:20:14 PST
We analyze the material transport equations (MTE) derived by Eslamian and co-authors and address the criticism expressed regarding the approach formulated in our previous work. In doing so, we show that the MTE formulated by Eslamian and co-authors are valid only in closed stationary non-isothermal systems in combination with the restrictions on the Onsager coefficients formulated in our work which is criticized, and that for nonstationary systems the approach we took can be used.
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Semen N. Semenov et al.Dynamic Passivation with BSA Overcomes LTCC Mediated Inhibition of PCRhttp://scholarworks.boisestate.edu/chem_facpubs/79
http://scholarworks.boisestate.edu/chem_facpubs/79Wed, 24 Oct 2012 11:44:32 PDT
The increasing use of low temperature co-fired ceramic (LTCC) for the fabrication of biological microfluidic devices necessitates further research on LTCC biocompatibility. In this study we explore the inhibitory effect of DuPont's 951 LTCC on Polymerase Chain Reaction (PCR), and demonstrate a novel mechanism to increase biocompatibility between LTCC and PCR with the addition of a common passivation substance, bovine serum albumin (BSA). We show that DuPont's 951 LTCC binds negatively charged proteins including BSA and ovalbumin (OVA). This is a significant discovery as proteins (enzymes) are an essential component of most biological reactions, and a frequent addition to microfluidic devices. A proposed model for LTCC inhibition of PCR by enzyme adsorption is presented.
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Jason Besecker et al.Predicted Structure and Binding Motifs of Collagen a1(Xi)http://scholarworks.boisestate.edu/chem_facpubs/78
http://scholarworks.boisestate.edu/chem_facpubs/78Wed, 03 Oct 2012 12:15:31 PDT
The amino propeptide of collagen a1(XI) (NPP) has been shown to bind glycosaminoglycans and to form a dimer. While these are independent biochemical events, it is likely that dimerization facilitates the interaction with glycosaminoglycans or alternatively, that glycosaminoglycan interaction facilitates the formation of an NPP:NPP dimer. The computer program MODELLER was used to generate a homology model of the collagen a1(XI) NPP monomer using the crystal structure of the closely related noncollagenous-4 (NC4) domain of collagen a1(IX) (PDB:2UUR) as the template. Additionally, a dimer model of collagen a1(XI) NPP domain was created based upon the thrombospondin dimer template (PDB:1Z78). The structure of the dimer created in MODELLER was validated by comparison to a dimer model generated by docking two monomers of PDB:2UUR using ClusPro. Calculations of relative binding energy for the interaction between each collagen 1(XI) NPP model and glycosaminoglycans as ligands was performed using AutoDock4. Computational results support a higher affinity between heparan sulfate and a dimer compared to a monomer. These findings are supported by affinity chromatography experiments in which distinct monomer and dimer peaks were observed. Sequentialvpoint mutation studies of the putative binding site (147-KKKITK-152) indicated the importance of the basic lysine residue for binding to heparan sulfate. Two orders of magnitude change in binding affinity was predicted when comparing wild type to the mutation K152A. Experimental data supports the predicted change in affinity.
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Julia Oxford et al.Comment on "Soret Motion in Non-Ionic Binary Molecular Mixtures" [J. Chem. Phys. 135, 054102 (2011)]http://scholarworks.boisestate.edu/chem_facpubs/77
http://scholarworks.boisestate.edu/chem_facpubs/77Thu, 27 Sep 2012 11:49:56 PDT
The material transport equations derived in the article by Leroyer and Würger [J. Chem. Phys. 135, 054102 (2011)10.1063/1.3615954] do not adequately provide a description of material transport in liquid binary systems. An alternate approach based on non-equilibrium thermodynamics is presented.
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Semen N. Semenov et al.Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educatorshttp://scholarworks.boisestate.edu/chem_facpubs/76
http://scholarworks.boisestate.edu/chem_facpubs/76Fri, 27 Jul 2012 11:47:04 PDT
We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms.
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Reed B. Jacob et al.